On the origin of low‐density neutrophils Hassani, Marwan; Hellebrekers, Pien; Chen, Na ...
Journal of leukocyte biology,
20/May , Letnik:
107, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Here we elaborate on the origin of low(er)‐density neutrophils (LDNs) to better understand the variation found in literature. Supplemented with original data, we test the hypothesis that buoyant ...density of neutrophils is characterized by a spectrum that as a whole shifts to a lower density after activation. Both the 20% highest density (HDNs) and 20% lowest density (LDNs) neutrophils from healthy donors were isolated by Percoll of different densities. Using this method we found that LDNs were significantly better in T‐cell suppression and bacterial containment than their 20% highest density counterparts. We found no statistically relevant differences in neutrophil survival or bacterial phagocytosis. Stimulation of healthy donor neutrophils with N‐formyl‐methionyl‐leucyl‐phenylalanine induced LDNs co‐segregating with peripheral blood mononuclear cells after Ficoll separation. These in vitro induced LDNs showed increased activation markers compared to HDNs and were comparable to the activation markers found on the LDN fraction seen in patients with chronic inflammatory conditions such as present in cancer patients. This all fits with the hypothesis that the density of neutrophils is distributed in a spectrum partially coupled to maturation. Additionally a shift in this spectrum can be induced by in vitro stimulation or by activation in disease.
Nowadays the term low(er) density neutrophils (LDN) is used to describe a specific subset of neutrophils with a certain buoyant density, but these LDNs are characterized by a wide variety in both functional and morphologic properties, especially in disease.
To compare re-rupture rate, complication rate, and functional outcome after operative versus nonoperative treatment of Achilles tendon ruptures; to compare re-rupture rate after early and late full ...weight bearing; to evaluate re-rupture rate after functional rehabilitation with early range of motion; and to compare effect estimates from randomised controlled trials and observational studies.
Systematic review and meta-analysis.
PubMed/Medline, Embase, CENTRAL, and CINAHL databases were last searched on 25 April 2018 for studies comparing operative versus nonoperative treatment of Achilles tendon ruptures.
Randomised controlled trials and observational studies reporting on comparison of operative versus nonoperative treatment of acute Achilles tendon ruptures.
Data extraction was performed independently in pairs, by four reviewers, with the use of a predefined data extraction file. Outcomes were pooled using random effects models and presented as risk difference, risk ratio, or mean difference, with 95% confidence interval.
29 studies were included-10 randomised controlled trials and 19 observational studies. The 10 trials included 944 (6%) patients, and the 19 observational studies included 14 918 (94%) patients. A significant reduction in re-ruptures was seen after operative treatment (2.3%) compared with nonoperative treatment (3.9%) (risk difference 1.6%; risk ratio 0.43, 95% confidence interval 0.31 to 0.60; P<0.001; I
=22%). Operative treatment resulted in a significantly higher complication rate than nonoperative treatment (4.9%
1.6%; risk difference 3.3%; risk ratio 2.76, 1.84 to 4.13; P<0.001; I
=45%). The main difference in complication rate was attributable to the incidence of infection (2.8%) in the operative group. A similar reduction in re-rupture rate in favour of operative treatment was seen after both early and late full weight bearing. No significant difference in re-rupture rate was seen between operative and nonoperative treatment in studies that used accelerated functional rehabilitation with early range of motion (risk ratio 0.60, 0.26 to 1.37; P=0.23; I
=0%). No difference in effect estimates was seen between randomised controlled trials and observational studies.
This meta-analysis shows that operative treatment of Achilles tendon ruptures reduces the risk of re-rupture compared with nonoperative treatment. However, re-rupture rates are low and differences between treatment groups are small (risk difference 1.6%). Operative treatment results in a higher risk of other complications (risk difference 3.3%). The final decision on the management of acute Achilles tendon ruptures should be based on patient specific factors and shared decision making. This review emphasises the potential benefits of adding high quality observational studies in meta-analyses for the evaluation of objective outcome measures after surgical treatment.
Liver cirrhosis is associated with osteoporosis, imbalance leading to falls, and subsequent fragility fractures. Knowing the prognosis of patients with liver cirrhosis of varying severity at the time ...of hip fracture would help physicians determine the course of treatment in this complex patient popultaion.
(1) Is there an association between liver cirrhosis of varying severity and mortality in patients with hip fractures? (2) Is there an association between liver cirrhosis of varying severity and the in-hospital, 30-day, and 90-day postoperative complications of symptomatic thromboembolism and infections including wound complications, pneumonia, and urinary tract infections?
Between 2015 and 2019, we identified 128 patients with liver cirrhosis who were treated for hip fractures at one of two Level I trauma centers. Patients younger than 18 years, those with incomplete medical records, fractures other than hip fractures or periprosthetic hip fractures, noncirrhotic liver disease, status after liver transplantation, and metastatic cancer other than hepatocellular carcinoma were excluded. Based on these exclusions, 77% (99 of 128) of patients were eligible; loss to follow-up was 0% within 1 year and 4% (4 of 99) at 2 years. The median follow-up duration was 750 days (interquartile range 232 to 1000). Ninety-four patients were stratified based on Model for End-stage Liver Disease (MELD) score subgroup (MELD scores of 6-9 MELD6-9, 10-19 MELD10-19, and 20-40 MELD20-40), and 99 were stratified based on compensation or decompensation status, both measures for liver cirrhosis severity. MELD scores combine laboratory parameters related to liver disease and are used to predict cirrhosis-related mortality based on metabolic abnormalities. Decompensation, however, is the clinical finding of acute deterioration in liver function characterized by ascites, hepatic encephalopathy, and variceal hemorrhage, associated with increased mortality. MELD analyses excluded 5% (5 of 99) of patients due to missing laboratory values. Median age at the time of hip fracture was 69 years (IQR 62 to 78), and 55% (54 of 99) of patients were female. The primary outcome of mortality was determined at 90 days, 1 year, and 2 years after surgery. Secondary outcomes were symptomatic thromboembolism and infections, defined as any documented surgical wound complications, pneumonia, or urinary tract infections requiring treatment. These were determined by chart review at three timepoints: in-hospital and within 30 days or 90 days after discharge. The primary outcome was assessed using a Cox proportional hazard analysis for the MELD score and compensation or decompensation classifications; secondary outcomes were analyzed using the Fisher exact test.
Patients in the MELD20-40 group had higher 90-day (hazard ratio 3.95 95% CI 1.39 to 12.46; p = 0.01), 1-year (HR 4.12 95% CI 1.52 to 11.21; p < 0.001), and 2-year (HR 3.65 95% CI 1.68 to 7.93; p < 0.001) mortality than those in the MELD6-9 group. Patients with decompensation had higher in-hospital (9% versus 0%; p = 0.04), 90-day (HR 3.35 95% CI 1.10 to 10.25; p = 0.03), 1-year (HR 4.39 95% CI 2.02 to 9.54; p < 0.001), and 2-year (HR 3.80 95% CI 2.02 to 7.15; p < 0.001) mortality than did patients with compensated disease. All in-hospital deaths were related to liver failure and within 30 days of surgery. The 1-year mortality was 55% for MELD20-40 and 53% for patients with decompensated disease, compared with 16% for patients with MELD6-9 and 15% for patients with compensated disease. In both the MELD and (de)compensation analyses, in-hospital and postdischarge 30-day symptomatic thromboembolic and infectious complications were not different among the groups (all p > 0.05). Ninety-day symptomatic thromboembolism was higher in the MELD20-40 group compared with the other two MELD classifications (13% for MELD20-40 and 0% for both MELD6-9 and MELD10-19; p = 0.02).
The mortality of patients with preexisting liver cirrhosis who sustain a hip fracture is high, and it is associated with the degree of cirrhosis and decline in liver function, especially in those with signs of decompensation, defined as ascites, hepatic encephalopathy, and variceal hemmorrhage. Patients with mild-to-moderate cirrhosis (MELD score < 20) and those with compensated disease may undergo routine fracture treatment based on their prognosis. Those with severe (MELD score > 20) or decompensated liver cirrhosis should receive multidisciplinary, individualized treatment, with consideration given to palliative and nonsurgical treatment given their high risk of death within 1 year after surgery.
Level III, therapeutic study.
Although the phrase "time is fascia" is well acknowledged in the case of necrotizing soft tissue infections (NSTIs), solid evidence is lacking. The aim of this study is to review the current ...literature concerning the timing of surgery in relation to mortality and amputation in patients with NSTIs.
A systematic search in PubMed/MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Cochrane Controlled Register of Trials (CENTRAL) was performed. The primary outcomes were mortality and amputation. These outcomes were related to the following time-related variables: (1) time from onset symptoms to presentation; (2) time from onset symptoms to surgery; (3) time from presentation to surgery; (4) duration of the initial surgical procedure. For the meta-analysis, the effects were estimated using random-effects meta-analysis models.
A total of 109 studies, with combined 6051 NSTI patients, were included. Of these 6051 NSTI patients, 1277 patients died (21.1%). A total of 33 studies, with combined 2123 NSTI patients, were included for quantitative analysis. Mortality was significantly lower for patients with surgery within 6 h after presentation compared to when treatment was delayed more than 6 h (OR 0.43; 95% CI 0.26-0.70; 10 studies included). Surgical treatment within 6 h resulted in a 19% mortality rate compared to 32% when surgical treatment was delayed over 6 h. Also, surgery within 12 h reduced the mortality compared to surgery after 12 h from presentation (OR 0.41; 95% CI 0.27-0.61; 16 studies included). Patient delay (time from onset of symptoms to presentation or surgery) did not significantly affect the mortality in this study. None of the time-related variables assessed significantly reduced the amputation rate. Three studies reported on the duration of the first surgery. They reported a mean operating time of 78, 81, and 102 min with associated mortality rates of 4, 11.4, and 60%, respectively.
Average mortality rates reported remained constant (around 20%) over the past 20 years. Early surgical debridement lowers the mortality rate for NSTI with almost 50%. Thus, a sense of urgency is essential in the treatment of NSTI.
Background
The aim of this study was to investigate which histopathologic findings are most indicative for necrotizing soft tissue infections (NSTIs) in ambivalent cases.
Methods
Patients undergoing ...surgical exploration for suspected NSTIs with obtainment of incisional biopsies for histopathological assessment were included from January 2013 until August 2019. The frozen sections and formalin-fixed paraffin-embedded (FFPE) samples were retrospectively re-assessed. The primary outcome was the discharge diagnosis.
Results
Twenty-seven (69%) biopsies of the 39 included samples were from patients with NSTIs. Microscopic bullae (
p
= 0.043), severe fascial inflammation (
p
< 0.001) and fascial necrosis (
p
< 0.001) were significantly more often present in the NSTI group compared to the non-NSTI group. Muscle edema (
n
= 5), severe muscle inflammation (
n
= 5), muscle necrosis (
n
= 8), thrombosis (
n
= 10) and vasculitis (
n
= 5) were most frequently only seen in the NSTI group. In thirteen tissues samples, there were some discrepancies between the severity of findings in the frozen section and the FFPE samples. None of these discrepancies resulted in a different diagnosis or treatment strategy.
Conclusion
Microscopic bullae, severe fascial or muscle inflammation, fascial or muscle necrosis, muscle edema, thrombosis and vasculitis upon histopathological evaluation all indicate a high probability of a NSTI. At our institution, diagnosing NSTIs is aided by using intra-operative frozen section as part of triple diagnostics in ambivalent cases. Based on the relation between histopathologic findings and final presence of NSTI, we recommend frozen section for diagnosing NSTIs in ambivalent cases.
In recent years, there has been a growing interest in operative treatment for multiple rib fractures and flail chest. However, to date, there is no comprehensive study that extensively focused on the ...incidence of complications associated with rib fracture fixation. Furthermore, there is insufficient knowledge about the short- and long-term outcomes after rib fracture fixation.
This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The MEDLINE, EMBASE, and Cochrane databases were searched to identify studies reporting on complications and/or outcome of surgical treatment after rib fractures. Complications were subdivided into (1) surgery- and implant-related complications, (2) bone-healing complications, (3) pulmonary complications, and (4) mortality.
Forty-eight studies were included, with information about 1,952 patients who received rib fracture fixation because of flail chest or multiple rib fractures. The overall risk of surgery- and implant-related complications was 10.3%, with wound infection in 2.2% and fracture-related infection in 1.3% of patients. Symptomatic nonunion was a relatively uncommon complication after rib fixation (1.3%). Pulmonary complications were found in 30.9% of patients, and the overall mortality was 2.9%, of which one third appeared to be the result of the thoracic injuries and none directly related to the surgical procedure. The most frequently used questionnaire to assess patient quality of life was the EuroQol-5D (EQ-5D) (n = 4). Four studies reporting on the EQ-5D had a weighted mean EQ-5D index of 0.80 indicating good quality of life after rib fracture fixation.
Surgical fixation can be considered as a safe procedure with a considerably low complication risk and satisfactory long-term outcomes, with surgery- and implant-related complications in approximately 10% of the patients. However, the clinically most relevant complications such as infections occur infrequently, and the number of complications requiring immediate (surgical) treatment is low.
Systematic Review, level III.
Background
It is unclear what the exact short-term outcomes of necrotizing soft tissue infections (NSTIs), also known and necrotizing fasciitis of the upper extremity, are and whether these are ...comparable to other anatomical regions. Therefore, the aim of this study is to assess factors associated with mortality within 30-days and amputation in patients with upper extremity NSTIs.
Methods
A retrospective study over a 20-year time period of all patients treated for NSTIs of the upper extremity was carried out. The primary outcomes were the 30-day mortality rate and the amputation rate in patients admitted to the hospital for upper extremity NSTIs.
Results
Within 20 years, 122 patients with NSTIs of the upper extremity were identified. Thirteen patients (11%) died and 17 patients (14%) underwent amputation. Independent risk factors for mortality were an American Society of Anesthesiologists (ASA) classification of 3 or higher (OR 9.26, 95% CI 1.64–52.31) and a base deficit of 3 meq/L or greater (OR 10.53, 95% CI 1.14–96.98). The independent risk factor for amputation was a NSTI of the non-dominant arm (OR 3.78, 95% CI 1.07–13.35). Length of hospital stay was 15 (IQR 9–21) days.
Conclusion
Upper extremity NSTIs have a relatively low mortality rate, but a relatively high amputation rate compared to studies assessing NSTIs of all anatomical regions. ASA classification and base deficit at admission predict the prognosis of patients with upper extremity NSTIs, while a NSTI of the non-dominant side is a risk factor for limb loss.
Background
Cricothyroidotomy and surgical tracheostomy are methods to secure airway patency. In emergency surgery, these methods are nowadays mostly reserved for patients unsuited for percutaneous ...procedures. Detailed description of complications and functional outcomes following both procedures is underreported in current literature. The aim of this study was to evaluate outcomes following cricothyroidotomy and tracheostomy in this presumed complex population.
Methods
In this retrospective cohort study, adult emergency surgical patients treated with cricothyroidotomy and/or surgical tracheostomy were included. Postoperative complications and functional outcomes in trauma and non-trauma patients were evaluated.
Results
Forty-one trauma patients and 11 non-trauma emergency surgical patients (mainly after elective onco-abdominal or vascular surgery) were included. Of 52 patients, seven underwent cricothyroidotomy pre-tracheostomy. Mortality was higher in non-trauma patients (
p
= 0.04) following both procedures. Over half of patients (56%,
n
= 29) regained unsupported airway patency with a tendency toward increased tracheostomy removal in trauma patients. Among complications, only pneumonia occurred frequently (60%,
n
= 31), with no relation to patient type. Other complications included local infection (5.8%,
n
= 4) and wound dehiscence (1.9%,
n
= 1). Adverse functional outcomes were frequently observed and were mild and self-limiting. Cervical spinal cord injury reduced overall unsupported airway patency (
p
= 0.01); with high cervical spinal cord injury related to adverse functional outcomes and increased home ventilation need.
Conclusions
No major procedure-related complications or functional adverse events were encountered following cricothyroidotomy and surgical tracheostomy, even though only complex patients were included. Only mild, self-limiting functional problems occurred, especially in trauma patients with cervical injury who underwent early tracheostomy by longitudinal incision. This information can aid clinicians in making tailor-made decisions for individual patients.
Purpose
The aim of this systematic review and meta-analysis was to present current evidence on rib fixation and to compare effect estimates obtained from randomized controlled trials (RCTs) and ...observational studies.
Methods
MEDLINE, Embase, CENTRAL, and CINAHL were searched on June 16th 2017 for both RCTs and observational studies comparing rib fixation versus nonoperative treatment. The MINORS criteria were used to assess study quality. Where possible, data were pooled using random effects meta-analysis. The primary outcome measure was mortality. Secondary outcome measures were hospital length of stay (HLOS), intensive care unit length of stay (ILOS), duration of mechanical ventilation (DMV), pneumonia, and tracheostomy.
Results
Thirty-three studies were included resulting in 5874 patients with flail chest or multiple rib fractures: 1255 received rib fixation and 4619 nonoperative treatment. Rib fixation for flail chest reduced mortality compared to nonoperative treatment with a risk ratio of 0.41 (95% CI 0.27, 0.61,
p
< 0.001,
I
2
= 0%). Furthermore, rib fixation resulted in a shorter ILOS, DMV, lower pneumonia rate, and need for tracheostomy. Results from recent studies showed lower mortality and shorter DMV after rib fixation, but there were no significant differences for the other outcome measures. There was insufficient data to perform meta-analyses on rib fixation for multiple rib fractures. Pooled results from RCTs and observational studies were similar for all outcome measures, although results from RCTs showed a larger treatment effect for HLOS, ILOS, and DMV compared to observational studies.
Conclusions
Rib fixation for flail chest improves short-term outcome, although the indication and patient subgroup who would benefit most remain unclear. There is insufficient data regarding treatment for multiple rib fractures. Observational studies show similar results compared with RCTs.
The risk of major bleeding complications in catheter directed thrombolysis (CDT) for acute limb ischemia (ALI) remains high, with reported major bleeding complication rates in up to 1 in every 10 ...treated patients. Fibrinogen was the only predictive marker used for bleeding complications in CDT, despite the lack of high quality evidence to support this. Therefore, recent international guidelines recommend against the use of fibrinogen during CDT. However, no alternative biomarkers exist to effectively predict CDT-related bleeding complications. The aim of the POCHET biobank is to prospectively assess the rate and etiology of bleeding complications during CDT and to provide a biobank of blood samples to investigate potential novel biomarkers to predict bleeding complications during CDT.
The POCHET biobank is a multicentre prospective biobank. After informed consent, all consecutive patients with lower extremity ALI eligible for CDT are included. All patients are treated according to a predefined standard operating procedure which is aligned in all participating centres. Baseline and follow-up data are collected. Prior to CDT and subsequently every six hours, venous blood samples are obtained and stored in the biobank for future analyses. The primary outcome is the occurrence of non-access related major bleeding complications, which is assessed by an independent adjudication committee. Secondary outcomes are non-major bleeding complications and other CDT related complications. Proposed biomarkers to be investigated include fibrinogen, to end the debate on its usefulness, anti-plasmin and D-Dimer.
The POCHET biobank provides contemporary data and outcomes of patients during CDT for ALI, coupled with their blood samples taken prior and during CDT. Thereby, the POCHET biobank is a real world monitor on biomarkers during CDT, supporting a broad spectrum of future research for the identification of patients at high risk for bleeding complications during CDT and to identify new biomarkers to enhance safety in CDT treatment.
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